Abstract
BackgroundDue to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation.MethodsA novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously prefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were then seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by augmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional assessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo.ResultsFor bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental group) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve than AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher bladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain number of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated into smooth muscle cells.ConclusionsThe AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and improved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the survival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder defects in the clinic in the future.
Highlights
Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with Adipose-derived stem cell (ASC) to promote bladder regeneration and restore bladder function
Evaluation of bladder acellular matrix grafts (BAMG)-Silk fibroin (SF) and autologous myofibroblast (AM)-SF scaffolds With the gradual increase in implantation time, the BAMG-SF was surrounded by the subcutaneous connective tissue (Fig. 1a)
The results revealed that the number of de novo SM22α-positive smooth muscle bundles supported by the AM-SF-ASC scaffolds was significantly higher than that supported by the AM-SF scaffolds (20.13 ± 10.43% versus 7.37 ± 1.59%, p < 0.05)
Summary
Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. The low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation. A variety of synthetic polymers and biological materials have been applied to facilitate bladder defect repair [2,3,4]. The specific mechanism by which ASCs promote bladder regeneration remains unclear [16]
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